2-(1,3,3-trimethylureido)-1,3,4-thiadiazole-5-n,n-dimethylsulfonamide

ABSTRACT

THE INDUSTRIAL HERBICIDE 5 - (1,3,3 - TRIMETHYLUREIDO)N,N - DIMETHYL - 1,3,4 - THIADIAZOLE - 2-SULFONAMIDE AND OTHER COMPOUNDS OF SIMILAR STRUCTURE MAY BE MADE BY A NOVEL PROCEDURE IN WHICH THE FIRST STEP IS THE OXIDATIVE CHLORINATION OF A 2-ALKYLAMINO-5-MERCAPTO-1,3,4-THIADIAZOLE TO YIELD THE CORRESPONDING SULFONYL CHLORIDE. THE SUBJECT COMPOUND WHICH PROCESSES FIVE METHYL SUBSTITUENT GROUPS IS MORE EFFECTIVE AS A HERBICIDE THAN COMPOUNDS WHICH CONTAIN OTHER ALKYL SUBSTITUENTS OR A LESSER NUMBER OF METHYL SUBSTITUENTS.

United States Patent 3,824,247 2-(1,3,3-TRlMETHYLURElD0)-1,3,4-THIADIAZOLE- -N,N-DIMETHYLSULFONAMIDE William C. Doyle, Jr., Leawood, and Loren W. Hedrich, Overland Park, Kans., assignors to Gulf Research &

Development Company, Pittsburgh, Pa.

No Drawing. Continuation-impart of application Ser. No. 119,417, Feb. 26, 1971. This application Sept. 1, 1971, Ser. No. 177,178

Int. Cl. C0711 91/62 US. Cl. 260-3063 D 1 Claim ABSTRACT OF THE DISCLOSURE This application is a coninuation-in-part of U5. Ser. No. 119,417 filed Feb. 26, 1971. The disclosure of the aforementioned application is incorporated herein by reference.

DESCRIPTION OF THE INVENTION U.S. Ser. No. 119,417 which is incorporated herein by reference discloses a new class of highly phytotoxic substances which may be applied to the locus of unwanted vegetation to effect control, either preor post-emergently. Eifective compounds have the structural formula:

in which R and R are selected from hydrogen, lower cycloalkyl, lower alkyl, alkoxy, cyanoalkyl, aralkyl, al koxyalkyl, alkylaminoalkyl, lower alkenyl and lower al kynyl substutients and heterocyclic structures in which R and R are together alkylene or oxyalkylene with two to five carbon atoms, R is hydrogen, methyl or ethyl, R is hydrogen or lower alkyl, R is selected from lower alkyl, lower alkenyl and lower cycloalkyl substituents and X is oxygen or sulfur.

In the aforementioned application many specific compounds of the class are disclosed having a high degree of phytotoxicity and varied selectivity. It has been discovered that one of the compounds of this class, 5-(1,3,3- trimethylureido) N,N dimethyl 1,3;4 thiadiazole-2- sulfonamide, is an unusually efiective herbicide of the type which is used industrially to prevent growth of weeds in railroad right-of-ways and in other areas where uncontrolled growth of vegetation is undesirable. In the aforementioned application, methods of synthesis of the new herbicides are also disclosed. A new, more direct method of synthesis of this class of herbicides has been discovered in which it has been found unnecessary to protect a free amino substituent on the thiadiazole nucleus during oxidative chlorination. The method of synthesis of the class of herbicides and use of a superior member of the class to control a large number of species of plant life are specifically exemplified below.

Herbicide Synthesis On the basis of disclosures in the chemical literature, particularly Roblin and Clapp, (J. Am. Chem. Soc. 72

4890 (1950)), the presence of a free amine function oil the thiadiazole molecule precludes the conversion of the mercapto group to the corresponding sulfonyl chloride by oxidative chlorination. Oxidative chlorination is a well known technique, most conveniently operated by introducing chlorine into dilute aqueous hydrochloric acid reaction medium at room temperature or below, with the substance to be clorinated present in solution or suspension. (See, for example, the publication by Petrow et al. J. Chem. Soc. 198, p. 1508). Amines are known to interfere with the reaction. Consequently a preferred approach to synthesis of the desired class of compounds has involved protection of the free amine group prior to oxidative chlorination, as shown below in the synthesis scheme which was disclosed in US. Ser. No. 119,417:

IINaOH S ll T in which R may be methyl or ethyl to yield a corresponding sulfonyl chloride having the structural formula (ll-E /S ifal H (b) reacting the sulfonyl chloride produced in step (a) with a secondary amine of the structural formula in which R may be hydrogen or lower alkyl and R may be hydrogen or lower alkyl or R and R together form a ring with the nitrogen atom to yield a sulfonamide having the structural formula 1 1? s t hit r (c) reacting the sulfonamide produced in step (b) with a carbamyl chloride or isocyanate having one of the structural formulae /s ii-E-r/ t1 1 R.

More specifically, the route to a superior industrial type herbicide composition is shown in the following scheme, in which alternate methods of carbamylation are outlined.

S I l T (CHa)zN-C O (Ill/Nail CH I 90-100 a)2N 2 NCON(CH;)

H C0012 N-N (in inert organic solvent 0 on. o (cmmPL l I( JCl t H T NN The synthesis of this compound is specifically exemplified as follows:

Preparation of 2-Methylamino-5-chlorosulfonyl- 1,3 ,4-t hiadiazole A rapid stream of chlorine is passed into a well stirred slurry of 55.0 g. (0.374 mols) of Z-methylamino-S-mercapto-1,3,4-thiadiazole in 1800 ml. of hydrochloric acid. While maintaining the temperature at 0 to (10) by cooling in an ice-salt bath, the chlorine addition is continued until no more chlorine is absorbed and the reaction mixture has a definite yellow color. Filtration of the solid and thorough washing with water gives 71.2 g. of Z-methylamino-S-chlorosulfonyl-1,3,4-thiadiazole, m.p. 87 (dec.).

Analysis.-Calcd: C, 31.80; H, 4.58; N, 21.19. Found: C, 31.59; H, 4.45; N, 21.44.

Preparation of 2-Methylamino-1,3,4-thiadiazole-5-N,N-

dimethylsulfonamide To a solution of 24.0 g. (0.133 mols) of 25% aqueous dimethylamine in 70 ml. dioxane is added slowly 2-methylamino 5 chlorosulfonyl 1,3,4-thiadiazole (the damp filter cake from oxidative chlorination of 9.5 g., 0.0645 mols, of 2-methylamino-5-mercapto-1,3,4-thiadiazole) while stiring in an ice bath. After an additional 1 to 2 hours stirring, the mixture is diluted 3- to 4-fold with water, filtered and the crystilline product washed with water. The 2 methylamino l,3,4-thiadiazole-5-N,N- dimethylsulfonarnide (70% overall yield from I) melts at 168-70".

Analysis.-Calcd: C, 27.00; H, 4.50; N, 25.25. Found; C, 26.79; H, 4.51; N, 25.13.

Preparation of 2-Ethylamino-1,3,4-thiadiazole-5-N- ethylsulfonamide Repeating the above procedure and reacting the damp filter cake (the dry product is unstable) from oxidative chlorination of 25.0 g. of Z-ethylamino-S-mercapto-1,3,4- thiadiazole with 19.0 g. of 70% aqueous ethylamine in 100 m1. of dioxane gave 17.9 g. of 2-ethylamino-1,3,4-thiadiazole-S-N-ethylsulfonamide, m.p. 137-9.

Preparation of 2-( 1,1,3-Trimethylureido)-1,3,4-thiadiazole-S-N,N-dimethylsulfonamide To a solution of 42.0 g. (0.19 mols) of 2-methylamino-1,3,4-thiadiazole-5 N,N dimethylsulfonamide in 225 ml. of dimethylformamide is added, with ice-bath cooling, 10.2 g. of a 57% oil dispersion of sodium hydride. After stirring 30 minutes at room temperature 20.4 g. (0.19 mole) of N,N-dimethylcarbamyl chloride is added slowly, without cooling, with the reaction temperature rising to about 55. The mixture is then heated to 90 for 3 hours, vacuum stripped, and the residue partitioned between benzene and water. The benzene layer is separated, evaporated and the residue is triturated with hexane to give 43 g. of 2-(1,3,3-trimethylureido)-l,3,4-thiadiazole- 5-N,N-dimethylsulfonamide, m.p. 103-5 The following method, based on simple, cheap raw materials is preferred for conversion of the amino-substituted thiadiazolesulfonamide to the corresponding ureido substituted compound.

Reaction of 2-Methylamino-l,3,4-thiadiazole-5,N,N-dimethylsulfonamide with Phosgene, and Dimethylamine Phosgene is bubbled into a well stirred slurry of 10.0 g. of Z-methylamino-1,3,4-thiadiazole-5-N,N-dimethylsulfonamide and ml. of dry toluene heated to 90-100. The solid starting material slowly dissolves and the phosgene addition is continued 30 minutes after a clear solution results. While maintaining the temperature at 90- 100 a rapid stream of nitrogen is passed through the solution for one hour to remove the excess phosgene. The toluene solution is filtered to remove a trace of gummy precipitate, cooled to 20-25 and 12.0 g. of 40% aqueous dimethylamine is added slowly, keeping the temperature below 30. The mixture is then heated to 5060 for 30 minutes, cooled, washed with two 100 ml. portions of water and the toluene is removed under vacuum. The crystalline residue is slurried with hexane and filtered to give 10.0 g. (76% yield) of 2-(l,3,3-dimethylureido)- 1,031,45- thiadiazole 5 N,N-dimethylsulfonamide, m.p. 1

Carrying out the reaction in the same way, except that the 2- methylamino 1,3,4 thiadiazole-5-N,N-dimethylsulfonamide was first converted to the hydrochloride in a stream of anhydrous hydrogen chloride gave a 78% yield of product, m.p. 1012.

Specific compounds which are illustrative of the class of herbicides which may be manufactured by the improved method of this invention are listed in Table I.

data are given. Compound No. 11 did not show a significant effect in either the preor post-emergency tests at either 1 lb. or 3 lb. per acre.

TABLE I R4 R: R1

II S /N-C--NT T-sOn i R:

as 0 3 Compound number groups R R R: Br n Melting point a C 1 H H H H CH 310. 2 H CH; H H CH: 227-228. 3 H CH: CHI H CH1 158-160. 3 CH: OH: H CH: 193-196 4 0H; CH; C H CH; 211-214. 5 CH: CHs OH: CH: CH; 103 105 0 32 2 2 5 C2 5 02H: (Iir%ui2%% B.P.

0 0.3mm. @3420 1 or i orrcul g g gg-ies.

4 v I -1s5. 1 H 1-0 H. H H CH 245-246 (1 o a omo 0H. 0H. H on: mes-21;. Be mp) 1 -CHaCHsOCH2CH: H H CH, 229 230 Combating Unwanted Vegetation 25 TABLE II Compound number 1 The novel herbicides are effective when used both post- M d I H n and pre-emergently. There is described below an illus- 0 60 gs ontrative procedure for herbicidal use of the compounds Plants pecies under controlled conditions 111 the greenhouse so as to C k 3113/80" 11b/acre obtain data on phytotoxic acivity and selectivity. gf gggggi 3 llglornlng glory, l 0 (1) wiii'iiicrvvraarii g g Wild mustard. I 1 0 An aqueous dispersion of each active compound was ggggygfgsgrassuu 0 0 prepared by combining 0.4 gram of the compound with Dowgy g 3 about 4 ml. of a solvent-emulsifier mixture (3 parts of a 0 0 commercial polyoxyethylated vegetable o1l emulsifier, one g 8 part xylene, one part kerosene) and then adding water, al zgtgg na. 0 0 with stirring, to a final volume of 40 ml. 40 mtalrah g g The 24 species of plants on which each compound was 1 o to be tested were planted in disposable plastic pots in a s i 1 8 greenhouse. Ten to eighteen days after emergence of the ggg z s 1 0 plants, three pots of each species were sprayed at each 5 3 rate with an aqueous dispersion of the active compound 523 g m" 0 0 prepared as described above, at rates of both 1 1b. and EIIIIIII: g 8 3 lb. of active compound per acre and at a spray volume of 60 gallons per acre. Approximately one week after the Mode -pp t on spray application the plants were observed and the rep Post sults rated according to the following schedule. Plant species 3lb./acre 1 lbJacre 3lb./ucre 11b./acre DEGREE OF EFFECT Compound umberz 0=no effect ggg ggbur 0 X 4 1-=slight elfect 2==moderate effect 3=severe elfect 4=maximum eflfect (all plants died) The same rating schedule was employed to judge preemergent results obtained according to the procedure below.

(2) Pre-Emergent Use A solution of each active compound was prepared by dissolving 290 mg. of the compound to be tested in 200 ml. of acetone. Disposable paper trays about 2 /2 inches deep were filled with soil and sprayed with the acetone solution at rates of 3 lb. and 1 lb. of active chemical per acre of sprayed area, were seeded with 24 species of plant seeds and were then covered with about /1 inch of soil. Twenty-one days after seeding and treatment the plantings were examined and herbicidal efiect was rated according to the above schedule.

Both post-emergent and pre-emergent results are set forth in Table II. Compound No. 1 did not show a significant herbicidal effect in the pre-emergence test and no Lambsquarter... Morning glory. Pigweed Wild mustard Barnyard grass Crabgrass- Downy broms. Giant ioxtail See footnotes at end of table.

TABLE II.-Contlnued Mode of application Pre Post Plant species 3 lb./acre 1 IbJaere 3 IbJacro 1 lbJacre Compound number 2 Green foxtall 4 3 4 3 3 0 0 4 4 4 1 4 4 1 3 4 3 4 4 4 3 4 4 3 1 4 2 4 4 4 4 4 4 4 4 4 4 4 4 Corn 4 2 1 0 Grain sorghum. 4 4 2 1 Rice 4 4 4 2 4 4 4 3 Compound number 4 Compound number 5 mianpiamwpppwmwwwptmhmmwpww wespwtawwwwwwmwlhwemawwthwppw pw-weopta u wpwwwowthwptaww-wwpw Compound number 6 Wild mustard-.. Barnyard grass. Crabgrass Downy br0me.. Giant toxtail.

Compound number 7 wwwo ONO

Pigweed See footnotes at end of table.

OHNO

TABLE IL- Contlnned Mode of application Plant species Pre Post

3 lb./acre 1 lb./acro 3 lbJacre 1 lb. lacre Compound number 7 Wild buckwheat Wild mustard... Barnyard grass. Crabgrass. Downy br0me Soybean... Sugar beets Tomato.

Corn Grain sorghum. Rice HQOQOOWQQOHHOOOHHWNOBH ococwwooccooooocwowo QOOOHHHOHHOCOQOOOONH QOOOOOOOQOOOOOOQOOOO Compound number 8 SOYDQHIL. Sugar beetswwmwmmmwwwmmcwmwwvhmmmwmw i-uowmwmcwmtcowmwuwmmpwpx Compound number 9 Cocklebur Lambsquartcr. Morning glory... Pigweed Wild buckwheat Wild mustard Barnyard grass Crabgrass Downy brome. Giant ioxtail. Green foxtail. Nutsedge Shattercane Wild oats Alfalfa Cotton Peanut Soybean Sugar beets Tomato Corn Grain sorghum Compound number 10 Cocklebur Lambsquarter Morning glory Pigweed Wild buckwheat Wild mustard Barnyard grass Crabgrass Downy brome. Giant foxtall... Green Ioxtail.

H' OO lFQQOQOQQ -NHWMOOK OWN OQOQHQCQQOOQQOOOOOOONOHN See footnotes at end of table.

OOQQNNHOOQQOQDOOOONHHQHN OOQOHHHQOODOOQQQOQOOOQON Compound number- TAB LE IV.Comparison of preemergent efiectiveness at 4 lb. per acre Mode of application Pre Post 3 lb./acre 3 lbJacre 1 IbJacre Plant Species 1 lbJaere TABLE II.Continued Plant species References Cited UNITED STATES PATENTS 2,820,794 1/1958 Young et a1. 260-306.8 D 4/1973 Cebalo 260--306.8 D

FOREIGN PATENTS 2,050,979 4/ 1971 Germany.

OTHER REFERENCES 70 Cebalo, Chem. Abstracts, 75 :49094w (1971).

R. GALLAGHER, Primary Examiner US. Cl. X.R. 75 71-90; 260247.1

1 A+101b./acre. A+5 lb./aere.

In the total scores tabulated above, compound No. 5

.l a r. m C m 44444004444444 4444234444 6 m m m 34.11 0003002111110011214 C C m m nnmnnnmmmmmmn .W N m 23333 21 23 a t 0 0 i m h z u d a a n m n mm nwnaw na a m w N Na 0 u D. \H 2 u n m S t u I s n w J m Wm nmwmmnuamw O S O Ma fl E Md N e a d mm m Wm mana e man m a H H in u n w an 2 m m EL .5 e 8 n th a H mm manannnmwanam MT W a 3 W1 m i a Z n w R R as aaamaaaaa 0 5 0 5 O 5 N I HHHHHH 2HHHHH 1 1 2 2 3 3 O R CCCCCCCCCCCO 1314 33010030004411440001 g S n e r t r. S .mmmmwm ww m TN H V t. a T S I 2 m m w r m N m m s m nnnnnoonnnnn .1 Stm n rS@ B J' N a as s 2 2424 44242340014413440012 H W m d M m 5 H HHH H n m m wmm m m R nnoHcooHHH H m M t u m w m m m 0 0 a 4 o 0 l u a t H m mzb p C11 n H N 2 n e 0 n t h Swa w C H d 04040031014024 4000131244 C 0 a w a T m D .o H w n e e s r m t e sh o H w w wammp m in; 231530 m m m m wd mm u W nnnnnmnomno m .wn s w R floccococnvcm .l e r 04140144444044 4100442444 M H m wiw m W 0% r 3 mw amwm m m mwm l mmm m m m m mflmum m PM R HHHCCCOHHHC H m V w m 6 .m m M .1 8 123345011131 u u S 0 5 b GHD. n b m c b u 0 4 C d u C b e o n e ad S o aymu n l mflv m m 8 a 0 t g m y N n m n e P n O u d 6 1 .l 3f T "a. ow fi mwmh I .r .0 n f m a H r 0 m 0 mmvwmm m=hom mnw m m N E I 8 n e C 21 O 1 d 0 mm nky m w mom ev. r m c bq dmu D H 0 hh a e ma E u ette m it k m w m Mm sd mt mm m m mm h flflm 1 N MmaVm a mrOr 0 M cLMPwwB vwkammdfn 0 P appears to also be fairly effective. However, over a period of several months the weed control obtained with compound No. 6 appears to remain nearly complete, while 5 3,726,892 with compound No. 5 there is a resurgence of weed growth. The reason becomes apparent when the two compounds are tested at lower application rates. Results obtained by comparing the two compounds at an application rate of A lb. per acre appear in Table IV. It is evident from these results that as the concentration of herbicide in the soil decreases, compound No. 5 becomes ineifective, while compound No. 6 continued to give complete control of a number of species. 

